Nrf2–ARE signaling in cellular protection: Mechanism of action and the regulatory mechanisms

• Published in: Journal of cellular physiology Vol. 235; no. 4; pp. 3119 - 3130
• Main Authors: Shaw, Pallab, Chattopadhyay, Ansuman
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2020
• Subjects: Animals; Antioxidants; Antioxidants - pharmacology; Homeostasis; Homeostasis - drug effects; Humans; Metals; NF-E2-Related Factor 2 - metabolism; Nrf2; Oxidants; Oxidative stress; Oxidative Stress - drug effects; Oxidizing agents; Regulatory mechanisms (biology); ROS; Signal Transduction - drug effects; stress response; Toxicants; Transcription; xenobiotic metabolizing enzymes; stress response; Nrf2; oxidative stress; ROS; xenobiotic metabolizing enzymes
• ISSN: 0021-9541; 1097-4652; 1097-4652
• DOI: 10.1002/jcp.29219

Oxidative stress is the increase in cellular oxidant concentration in comparison to antioxidant titer. Toxic insults and many other diseased conditions are mediated through the formation of such condition. Once the redox equilibrium is disrupted, the cellular antioxidant system functions to bring back the cell to redox homeostasis state. The field players of the cytoprotective machinery are the xenobiotic‐metabolizing enzymes that are transcriptionally controlled by upstream regulatory pathways like the Nrf2–ARE pathway and AhR–XRE pathway. The importance of Nrf2 lies in the fact that it is activated by a variety of compounds and has a wide range of inducers including metals, organic toxicants and so forth. The present review article aims to discuss the role of Nrf2 in cellular protection and also intends to illuminate the regulatory mechanisms that control Nrf2 itself. This can add to our knowledge of how the cell reacts and survives against such stressed conditions. Nrf2–ARE signaling pathway mediates cellular oxidative stress response. Nrf2 is a transcription factor that drives the transcription of various cytoprotective proteins. It is regulated by an intricate network of other proteins that ensure appropriate cellular stress response as a function punctual demands.